Rational Design, Synthesis, and Biological Evaluation of 7‑Azaindole Derivatives as Potent Focused Multi-Targeted Kinase Inhibitors

Efforts
were made to improve a series of potent dual ABL/SRC inhibitors
based on a 7-azaindole core with the aim of developing compounds that
demonstrate a wider activity on selected oncogenic kinases. Multi-targeted
kinase inhibitors (MTKIs) were then derived, focusing on kinases involved
in both angiogenesis and tumorigenesis processes. Antiproliferative
activity studies using different cellular models led to the discovery
of a lead candidate (6z) that combined both antiangiogenic
and antitumoral effects. The activity of 6z was assessed
against a panel of kinases and cell lines including solid cancers
and leukemia cell models to explore its potential therapeutic applications.
With its potency and selectivity for oncogenic kinases, 6z was revealed to be a focused MTKI that should have a bright future
in fighting a wide range of cancers.